Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis.
Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis.
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DOI：
10.1136/annrheumdis-2021-221664
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发表时间：
2022-06
影响因子：
27.4
通讯作者：
Banerjee, Subhashis
中科院分区：
文献类型：
--
作者：
Mease, Philip J.;Deodhar, Atul A.;van der Heijde, Desiree;Behrens, Frank;Kivitz, Alan J.;Neal, Jeffrey;Kim, Jonghyeon;Singhal, Shalabh;Nowak, Miroslawa;Banerjee, Subhashis
评估口服选择性酪氨酸激酶 2 (TYK2) 抑制剂 deucravacitinib 对活动性银屑病关节炎 (PsA) 患者的疗效和安全性。在这项双盲 II 期试验中，203 名 PsA 患者按 1:1:1 的比例随机分配至安慰剂组：deucravacitinib 6 mg 每天一次或 12 mg 每天一次。主要终点是第 16 周时的美国风湿病学会 (ACR-20) 反应。第 16 周时，与安慰剂 (31.8%) 相比，每天一次 6 mg deucravacitinib (52.9%，p=0.0134) 和每天 12 mg 一次 (62.7%，p=0.0004) 的 ACR-20 反应显着更高。与安慰剂相比，在健康评估问卷-残疾指数和简表 36 身体成分总结评分以及银屑病面积和严重性指数 75 反应中，多重控制的次要终点相对于基线的变化有显着改善 (p≤0.05)。 deucravacitinib 治疗的多个探索性终点也出现了改善。 deucravacitinib治疗的患者中最常见的不良事件（AE）（≥5%）是鼻咽炎、上呼吸道感染、鼻窦炎、支气管炎、皮疹、头痛和腹泻。 deucravacitinib 治疗没有出现严重的 AE，也没有出现带状疱疹、机会性感染和主要不良心血管事件，也没有出现与安慰剂相比实验室参数平均变化的差异。选择性 TYK2 抑制剂 deucravacitinib 治疗具有良好的耐受性，并且在 PsA 患者中的 ACR-20、多重控制次要终点和其他探索性疗效指标方面比安慰剂有更大的改善。有必要对 deucravacitinib 进行更大规模、更长时间的试验，以确认其在 PsA 中的安全性和益处。 NCT03881059。
To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16. ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p=0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (≥5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment. Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA. NCT03881059.
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DOI：
10.1038/nrdp.2016.82
发表时间：
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期刊：
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影响因子：
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